scholarly journals Emerging Role of Exosomes in Diagnosis and Treatment of Infectious and Inflammatory Bowel Diseases

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1111 ◽  
Author(s):  
Anaïs Larabi ◽  
Nicolas Barnich ◽  
Hang Thi Thu Nguyen

To communicate with each other, cells release exosomes that transfer their composition, including lipids, proteins and nucleic acids, to neighboring cells, thus playing a role in various pathophysiological processes. During an infection with pathogenic bacteria, such as adherent-invasive E. coli (AIEC) associated with Crohn disease, exosomes secreted by infected cells can have an impact on the innate immune responses of surrounding cells to infection. Furthermore, inflammation can be amplified via the exosomal shuttle during infection with pathogenic bacteria, which could contribute to the development of the associated disease. Since these vesicles can be released in various biological fluids, changes in exosomal content may provide a means for the identification of non-invasive biomarkers for infectious and inflammatory bowel diseases. Moreover, evidence suggests that exosomes could be used as vaccines to prime the immune system to recognize and kill invading pathogens, and as therapeutic components relieving intestinal inflammation. Here, we summarize the current knowledge on the role of exosomes in bacterial infections and highlight their potential use as biomarkers, vaccines and conveyers of therapeutic molecules in inflammatory bowel diseases.

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Anouk Waeytens ◽  
Martine De Vos ◽  
Debby Laukens

Inflammatory bowel diseases (IBDs) are a group of chronic, relapsing, immune-mediated disorders of the intestine, including Crohn's disease and ulcerative colitis. Recent studies underscore the importance of the damaged epithelial barrier and the dysregulated innate immune system in their pathogenesis. Metallothioneins (MTs) are a family of small proteins with a high and conserved cysteine content that are rapidly upregulated in response to an inflammatory stimulus. Herein, we review the current knowledge regarding the expression and potential role of MTs in IBD. MTs exert a central position in zinc homeostasis, modulate the activation of the transcription factor nuclear factor (NF)-B, and serve as antioxidants. In addition, MTs could be involved in IBD through their antiapoptotic effects or through specific immunomodulating extracellular effects. Reports on MT expression in IBD are contradictory but clearly demonstrate a deviant MT expression supporting the idea that these aberrations in IBD require further clarification.


2011 ◽  
Vol 11 ◽  
pp. 1536-1547 ◽  
Author(s):  
Donata Lissner ◽  
Britta Siegmund

Inflammasomes are intracellular multiprotein complexes that coordinate the maturation of interleukin (IL)-1β and IL-18 in response to pathogens and metabolic danger. Both cytokines have been linked to intestinal inflammation. However, recently evolving concepts ascribe a major role to the inflammasome in maintaining intestinal homeostasis. This review recapitulates its position in the development of inflammatory bowel disease, thereby outlining a model in which hypo- as well as hyperfunctionality can lead to an imbalance of the system, depending on the specific cell population affected. In the epithelium, the inflammasome is essential for regulation of permeability and epithelial regeneration through sensing of commensal microbes, while excessive inflammasome activation within the lamina propria contributes to severe intestinal inflammation.


2021 ◽  
Vol 18 (1) ◽  
pp. 20-29
Author(s):  
S. A. Bulgakov ◽  
G. M. Chernakova ◽  
E. A. Kleshcheva ◽  
S. V. Simonova

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases, which are often accompanied by inflammation of other organs. This article presents modern data on etiology, pathogenesis and clinical course of inflammatory bowel diseases, as well as information on extraintestinal eye manifestations of nonspecific ulcerative colitis and Crohn’s disease. The role of microbiota, genetic factors, immune system defects in pathogenesis of intestinal inflammation and extraintestinal eye manifestations is considered. The possibility the development of ophthalmopathology not only against the background of intestinal inflammation, but also as a consequence of therapeutic and surgical methods of treatment of ulcerative colitis and Crohn’s disease is noted. The peculiarities of the course of episcleritis/scleritis, keratitis, uveitis, chorioretinitis, optical neuritis for patients with inflammatory bowel diseases are considered. The presence of these complications may reflect the activity of the underlying disease, which in some cases requires correction of therapy. Anterior uveitis and episcleritis/scleritis are the most common extraintestinal manifestations of inflammatory bowel disease. Inflammation of tissues of the posterior segment of the eye and optic nerve against the background of ulcerative colitis and Crohn’s disease are less common, but are of clinical importance, as they can catastrophically damage the structures of the eye and, as a consequence, lead to complete blindness. Considering the possibility of mild clinical symptoms and asymptomatic course of inflammation in the eye envelopes, the importance of ophthalmological examination of all patients with ulcerative colitis and Crohn’s disease is emphasized. Aspects of modern therapy of ophthalmopathology and background intestinal inflammation are highlighted. Biological preparations — antagonists of pro-inflammatory cytokines — have been identified as the most promising in the treatment of inflammatory intestinal diseases and extraintestinal manifestations. The important role of proper nutrition and biologically active supplements containing omega-3 fatty acids, vitamin D, microelements, was noted as auxiliary therapy of both intestinal and extraintestinal inflammation.


2021 ◽  
Vol 11 (1) ◽  
pp. 68-78
Author(s):  
Yu. P. Uspenskiy ◽  
N. V. Baryshnikova ◽  
A. N. Suvorov ◽  
A. V. Svarval

Helicobacter pylori is detected in the human intestine on average in 35% of clinical cases, but the question about its etiopathogenetic role in intestinal diseases has not been fully investigated. Many scientists study a relationship between the H. pylori persistence and development of various bowel diseases. Diverse viewpoints have been proposed regarding a potential link between H. pylori and inflammatory bowel diseases (IBD). Here we review the data from domestic and foreign studies aimed at examining potential role of H. pylori both as a trigger and protector resulting in the pathogenetic alterations leading to developing Crohn‘s disease and ulcerative colitis. The former is favored by the hypothesis wherein H. pylori may trigger IBD due to potential connection between extragastric infection and its direct damaging action as well as indirect effects contributing to the initiation of oxidative stress, autoimmune aggression and development of intestinal dysbiosis. In addition, the effects of enterohepatic Helicobacter spp. promoting IBD pathogenesis are discussed. The mechanisms underlying the protective role of H. pylori infection may be driven via differentially expressed acute and/or chronic local inflammatory mucosal response able to downmodulate systemic immune responses and suppress autoimmune reactions, as well as skewing host immune response from a pro-inflammatory Th1/Th17 cell-mediated towards regulatory T-cell response. Moreover, it was found that H. pylori may induce production of antibacterial peptides counteracting potentially pathogenic bacteria involved in IBD pathogenesis. In particular, it was found that IBD patients are dominated with moderate active antral gastritis coupled to atrophy, with the peak intensity observed in patients under 30 years of age. Intensity of intestinal metaplasia in the gastric mucosa of IBD patients accounted for by the duration of the disease course. Basal IBD therapy with 5-aminosalicylic acid lowers severity and activity of gastritis, degree of atrophy as well as magnitude H. pylori invasion in the gastric mucosa. There is evidence that 5-aminosalicylic acid-containing drugs may result in a so-called “spontaneous eradication” of H. pylori infection. Extended investigations are required to examine a role of H. pylori in IBD pathogenesis.


2021 ◽  
pp. 16-19
Author(s):  
G. V. Lukina ◽  
P. I. Kulakova ◽  
A. A. Novikov ◽  
E. N. Alexandrova ◽  
N. A. Savenkova ◽  
...  

Background. Patients with inflammatory bowel diseases (IBD) often have lesions of the musculoskeletal system, which is an extra-intestinal manifestation and mainly belongs to the group of seronegative spondyloarthritis (SPA). Ankylosing spondylitis (AS) is one of the main forms of diseases from the group of spondyloarthritis, associated with IBD. The frequency of AS in patients with IBD is of interest for elucidating the general pathophysiology of diseases. Colonoscopy is required to diagnose intestinal pathology. Colonoscopy in patients with AS to detect IBD, especially in the absence of intestinal symptoms, is very diffcult. Mainly for the diagnosis of IBD, the defnition of fecal calprotectin is used. Recently, there has been an interest in serum calprotectin, an increase in which is associated with a higher activity of the disease and is a marker of the intensity of inflammation in the intestine. However, there is currently no consensus on the clinical signifcance for serum calprotectin.The aim. To evaluate the role of serum calprotectin in diagnosis of inflammatory bowel disease in patients with ankylosing spondylitis.Materials and methods. In the analysis were included 50 patients with AS, fulflling the modifed New York criteria, among them were 36 (72%) men and 14 (28%) women, the mean age of patients was 42.5 ± 9.9, mean disease duration was 13.4 ± 8.7 years. All patients were examined with ESR, CRP, FC (range: 100–1800 µg/g), esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the SC level using ELISA (Buhlmann MRP8/14 ELISA, range: 0.4–3.9 µg/ml).Results. All patients had a high disease activity, mean BASDAI was 5.3 ± 1.8, mean ASDAS CRP was 3.7 ± 1.01, mean ASDAS ESR was 3.6 ± 1.01. 78% patients had high FC level (more than 100 µg/g), while only 18% patients had an increase of SC level. IBD were diagnosed in 11 cases: 6 (12%) patients with CD and 5 (10%) patients with UC, in the remaining cases (78%) was no intestinal pathology. Only two patients with IBD had a high SC level. SC level was more correlated with ESR (r = 0.5) and CRP (r = 0.5) (p < 0.05) levels, than with FC level (r = 0.4) (p < 0.05).Conclusion. The results have shown that there was currently insuffcient data to assess the possibility of using SC in the diagnosis of IBD in patients with AS. There was a signifcant association between the SC, CRP and ESR, but not fecal calprotectin. Potentially SC may be more representative for systemic inflammation than intestinal inflammation.


2017 ◽  
Vol 24 (1) ◽  
pp. 123-135 ◽  
Author(s):  
Michele Biagioli ◽  
Andrea Mencarelli ◽  
Adriana Carino ◽  
Sabrina Cipriani ◽  
Silvia Marchianò ◽  
...  

Abstract Background The DNAX adaptor protein 12 (DAP12) is a transmembrane adaptor molecule that signals through the activation of Syk (Spleen Tyrosine Kinase) in myeloid cells. The purpose of this study is to investigate the role of DAP12 and Syk pathways in inflammatory bowel diseases (IBDs). Methods DAP12 deficient and DAP12 transgenic, overexpressing an increased amount of DAP12, mice and Syk deficient mice in the C57/BL6 background were used for these studies. Colitis was induced by administering mice with dextran sulfate sodium (DSS), in drinking water, or 2,4,6-trinitrobenzene sulfonic acid (TNBS), by intrarectal enema. Results Abundant expression of DAP12 and Syk was detected in colon samples obtained from Crohn’s disease patients with expression restricted to immune cells infiltrating the colonic wall. In rodents development of DSS colitis as measured by assessing severity of wasting diseases, global colitis score,and macroscopic and histology scores was robustly attenuated in DAP12-/- and Syk-/- mice. In contrast, DAP12 overexpression resulted in a striking exacerbation of colon damage caused by DSS. Induction of colon expression of proinflammatory cytokines and chemokines in response to DSS administration was attenuated in DAP12-/- and Syk-/- mice, whereas opposite results were observed in DAP12 transgenic mice. Treating wild-type mice with a DAP-12 inhibitor or a Syk inhibitor caused a robust attenuation of colitis induced by DSS and TNBS. Conclusions DAP12 and Syk are essential mediators in inflammation-driven immune dysfunction in murine colitides. Because DAP12 and Syk expression is upregulated in patients with active disease, present findings suggest a beneficial role for DAP12 and Syk inhibitors in IBD.


2021 ◽  
Vol 10 (4) ◽  
pp. 853
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Gian Ludovico Rapaccini ◽  
Antonio Gasbarrini ◽  
Alessandro Armuzzi ◽  
...  

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.


2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.


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